prevalence of gram negative bacteria in ventilator associated pneumonia in neonatal intensive care units a systematic review and meta analysis protocol

Open Access Protocol Prevalence of Gram-negative bacteria in ventilator-associated pneumonia in neonatal intensive care units: a systematic review and meta-analysis protocol Yousef Erfani,1 Arezoo Rasti,2 Leila Janani3 To cite: Erfani Y, Rasti A, Janani L Prevalence of Gramnegative bacteria in ventilatorassociated pneumonia in neonatal intensive care units: a systematic review and metaanalysis protocol BMJ Open 2016;6:e012298 doi:10.1136/ bmjopen-2016-012298 ▸ Prepublication history and additional material is available To view please visit the journal (http://dx.doi.org/ 10.1136/bmjopen-2016012298) Received 14 April 2016 Revised 15 September 2016 Accepted 19 September 2016 Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran Department of Biostatistics, School of Public health, Iran University of Medical Sciences, Tehran, Iran Correspondence to Dr Yousef Erfani; yerfani@sina.tums.ac.ir ABSTRACT Introduction: Ventilator-associated pneumonia (VAP) is a common and potentially lethal problem among mechanically ventilated neonates in neonatal intensive care units (NICUs) The main pathogenic bacteria of VAP in NICUs are Gram-negative pathogens, which show a general decline in sensitivities to commonly used antibiotics, but their true prevalence is not known Methods and analysis: We aim to provide a systematic review of studies measuring the prevalence of Gram-negative bacteria in VAP in NICUs We will search PubMed, SCOPUS, EMBASE and the ISI Web of Science, as well as the Google Scholar search engine with no restriction on language Full copies of articles will be identified by a defined search strategy and will be considered for inclusion against predefined criteria Study selection and data extraction will be performed by independent reviewers Statistical analysis will include the identification of data sources and documentation of estimates, as well as the application of the randomeffects and fixed-effects meta-analysis models This will allow us to aggregate prevalence estimates and account for between-study variability in calculating the overall pooled estimates and 95% CI for the prevalence of Gram-negative bacteria in VAP in NICUs Heterogeneity will be evaluated using the I2 and χ2 statistical tests to determine the extent of variation in effect estimates due to heterogeneity rather than chance Publication bias and data synthesis will be assessed by funnel plots and Begg’s and Egger’s tests using STATA software V.13 This systematic review protocol was prepared according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocols (PRISMA-P) 2015 Statement Ethics and dissemination: No ethical issues are predicted These findings will be published in a peerreviewed journal and presented at national and international conferences Trial registration number: CRD42016036048 INTRODUCTION Ventilator-associate pneumonia (VAP) is pneumonia in mechanically ventilated patients, and develops after the patient has Strengths and limitations of this study ▪ This is the first attempt as a systematic review to summarise the prevalence of Gram-negative bacteria in ventilator-associated pneumonia (VAP) in neonatal intensive care units (NICUs) ▪ We will include observational studies that used the US Centers for Disease Control and Prevention (CDC) and National Healthcare Safety Network (NHSN) definitions ▪ The study screening, data extraction and the risk of bias of the current study will be assessed independently by two researchers ▪ This study could potentially help policymakers and guideline developers in the management of neonates with VAP in NICUs ▪ This review is restricted to a neonatal population (8, respectively An independent investigator will be consulted through discussion to reach consensus where there is uncertainty or disagreement between reviewers An evaluation of the risk of bias will allow for sensitivity analysis Data synthesis All included studies will be overviewed and presented in two separate tables The first table will provide details on study quality according to the mentioned tool The other table will include study design, participants and the characteristics of isolated bacteria Our statistical analysis of the primary measures will include two steps: (1) identification of data sources and documenting estimates, and (2) using a random-effects and fixed-effects meta-analysis model to aggregate prevalence estimates and to account for variability between studies, by calculating the overall pooled estimate and the 95% CI Initially, the data will be analysed using a narrative method Heterogeneity will be evaluated to determine the extent of variation in effect estimates due to heterogeneity rather than chance The heterogeneity among the primary studies will be evaluated by the forest plots, χ2 test (with significance defined at the α-level of 10%) and I2 statistic The prevalence of Gram-negative bacteria in VAP in NICUs from different studies will be pooled through a meta-analysis using STATA V.13 statistical software (Stata Corp 2013 Stata Statistical Software: Release 13 College Station, Texas, USA: Stata Corp LP) Open Access Assessment of heterogeneity The heterogeneity among the included studies will be assessed using the I2 heterogeneity statistic, reported as a percentage (%), to determine the extent of variation among the studies.41 Categories of heterogeneity will be defined as follows: ≤25% low, 26–50% moderate, 51– 75% substantial and 76–100% as considerable, defined by Higgins Forest plots will also be used to further identify heterogeneity by means of the χ2 test (with significance defined at the α-level of 10%) and the I2 statistic (where ≥50% indicates substantial heterogeneity) Sensitivity analysis We will implement sensitivity analyses to explore the impacts of methodological quality and sample size on the robustness of review conclusions Meta-analyses will be repeated after excluding studies with lower methodological quality and studies with sample sizes much larger than those of other studies Sensitivity analyses will be reported in a summary table, and reviewed conclusions will be interpreted by making comparisons between the two meta-analyses Any discrepancies or disagreements will be discussed by the reviewers and, if necessary, they will call an independent reviewer to provide clarification Subgroup analyses Subgroup analyses will be conducted according to the region, gender and isolated Gram-negative bacteria manuscript YE and LJ will also screen potential studies, extract data and assess their quality Competing interests None declared Provenance and peer review Not commissioned; externally peer reviewed Data sharing statement All recorded data from the data extraction process will be available on request to the extent that it is not included in the systematic review article Open Access This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work noncommercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial See: http:// creativecommons.org/licenses/by-nc/4.0/ REFERENCES Assessment of reporting bias The publication bias will be assessed by funnel plots (ie, plots of study results against precision) and Begg’s and Egger’s tests 10 Reporting of this review We will make use of flow diagrams to summarise the inclusion criteria and selection process of studies, and also to detail the reasons for exclusion This systematic review will be reported according to the PRISMA 2009 guidelines.37 The search strategy and quality appraisal tool will also be published as online supplementary material documents 11 Ethics and 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